Virology

A genetically humanized mouse model for hepatitis C virus infection Dorner, M. et al. Nature 474, 208–211 (2011)

Dorner et al. have developed the first humanized mouse model, with a normal immune system, that can be infected with hepatitis C virus (HCV). The fact that mouse cells are resistant to HCV entry has been a major limitation in HCV research; HCV will only naturally infect chimpanzees and humans, possibly owing to a requirement for specific host cell factors. Previous work had shown that the minimal human factors that are required for HCV uptake by mouse cells are CD81 and occludin. The authors showed that mice expressing CD81 and occludin can be efficiently infected with HCV, although the infection was not sustained indefinitely. To confirm the utility of the model, the authors showed that HCV could be blocked by passive immunization with CD81-specific antibodies and that a vaccinia virus-based vaccine could be used to generate partial protection against HCV challenge.

Phage biology

Alternative mechanism for bacteriophage adsorption to the motile bacterium Caulobacter crescentus Guerro-Ferreira, R. C. et al. Proc. Natl Acad. Sci. USA 108, 9963–9968 (2011)

During infection, many bacteriophages initially adsorb to the flagellum and then interact with receptors on the cell pole. Guerro-Ferreira et al. used cryo-electron tomography to study the three-dimensional structures of the ΦCb13 and ΦCbK phages as they infect the bacterium Caulobacter crescentus. They found that ΦCb13 and ΦCbK have a novel mode of infection, as the initial interaction of the phages with the flagellum requires a filament on the phage head that wraps around the flagellum, allowing the phages to use flagellar rotation to draw themselves closer to host receptors at the cell pole. This mechanism may increase the chances of the bacteriophages being able to infect hosts such as C. crescentus, which normally exists at low densitites. The authors suggest that phage head filaments, which are poorly characterized elements of phage structures, may be generally involved in phage propagation.

HIV

The TRIM family protein KAP1 inhibits HIV-1 integration Allouch, A. et al. Cell Host Microbe 9, 484–495 (2011)

The HIV integrase enzyme catalyses the integration of the HIV genome into the host cell's DNA. The activity of integrase is enhanced through acetylation by host enzymes. To investigate the importance of integrase acetylation, Allouch et al. developed a yeast two-hybrid screen using acetylated integrase as bait. They identified KAP1 (also known as TRIM28) as a protein that preferentially binds acetylated integrase. Knocking down KAP1 using a small interfering RNA increased HIV integration, showing that KAP1 acts as a viral restriction factor. Using immunoprecipitation, the authors showed that KAP1 functions to decrease integrase acetylation by favouring the binding of histone deacetylase 1 (HDAC1) to integrase. The authors propose that KAP1 restricts HIV-1 by recruiting HDAC1 to integrase, leading to its deacetylation and the inhibition of integrase function.